DESCRIPTION: Bacterial infections of the teeth and gingiva commonly cause tooth decay and periodontal disease, but may also cause serious systemic diseases such as endocarditis. Vaccines have a demonstrated potential to prevent infectious diseases. Co-administration of antigen with an immune stimulant called an "adjuvant" is usually necessary to stimulate the development of protective immunity rather than tolerance, particularly in response to oral antigens. Bromelain is a natural mixture of proteinases derived from pineapple stem. Although ingestion of most proteins results in immune tolerance, our preliminary data show that bromelain generates strong systemic immune responses when administered orally. Thus bromelain may serve as a self-adjuvant for induction of anti-bromelain antibodies. Our data show that bromelain is inhibited by trapping in complexes with the broad spectrum proteinase inhibitor alpha-2-macroglobulin (alpha-2M). Alpha-2M complexes are efficiently taken up by receptors that are present on antigen-presenting cells. We posit that proteolytically active bromelain given orally interacts with alpha-2M in vivo to form complexes that efficiently induce immune responses. Based upon this hypothesis, antigens co-trapped with bromelain in alpha-2M complexes should also be strongly immunogenic. The Aim of this study is to investigate the role of bromelain proteolytic activity in induction of antibody responses against itself and co-administered antigens, using an oral vaccine against Dental pathogens in mice. Bromelain proteolytic activity will be increased by formulation in antacid or permanently inactivated by reduction and alkylation. Bromelain will be administered orally to mice mixed with or covalently linked to antigen. Specific serum IgG and salivary IgG and IgA antibody responses against bromelain and antigen will be determined. If these studies confirm the potential of bromelain as an adjuvant, preparations containing bromelain and a mixture of relevant antigens could be developed for periodic administration as "swish and swallow" vaccines to induce and maintain immunity against Dental pathogens.